Hiromichi Kanehiro

The serum interleukin 8 level reflects hepatic mitochondrial redox state in hyperthermochemohypoxic isolated liver perfusion with use of a venovenous bypass

BACKGROUNDnWe have recently developed a simple method of hyperthermochemohypoxic isolated liver perfusion (HILP) as a regional therapy for unrecognized liver micrometastases. However, little is known about the influence of HILP on cytokine production and liver function. We investigated the influence of HILP on interleukin 8 (IL-8) production and the hepatic mitochondrial function and assessed the relationship between these 2 parameters. We also measured the serum tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) levels to examine the involvement of HILP-induced cytokines in the tumor response.nnnMETHODSnSixteen patients with metastatic liver tumors were randomly assigned to undergo hepatectomy with HILP (group A, n = 9) or hepatectomy alone (group B, n = 7). The isolated liver was perfused for 30 minutes with Ringers lactate solution containing chemotherapeutic agents warmed to 42 degrees C to 43 degrees C without oxygenation.nnnRESULTSnThe serum IL-8 levels in group A were markedly increased, with peaks at 3 hours after reperfusion, which was significantly higher than levels in group B (P < .01). In group A the arterial ketone body ratio, which reflects the hepatic mitochondrial redox state, decreased during perfusion and was gradually restored to the preperfusion level 1 hour after reperfusion. However, in group B it decreased during hepatectomy but rapidly recovered 5 minutes after hepatectomy. There was a significant negative correlation between the peak serum IL-8 level and the initial velocity of arterial ketone body ratio recovery for the first 5 minutes after reperfusion r = -0.83, P < .001). The serum TNF-alpha and IL-1 beta were temporarily detected only in 3 of 9 patients in group A.nnnCONCLUSIONSnWe have shown that HILP resulted in augmented IL-8 release but not TNF-alpha and IL-1 beta and that the serum IL-8 level reflects the hepatic mitochondrial redox state. These findings suggest that IL-8 production may be associated with hepatic mitochondrial impairment during ischemia. This work may contribute to new therapeutic strategies not only for hepatic ischemia reperfusion injury but also for metastatic liver tumors.

Evaluation of initial hepatic allograft function with changes of free plasma amino acids in canine orthotopic liver transplantation

We investigated the correlation between amino acid level and hepatic graft function. Plasma amino acid levels were measured at three time periods during canine orthotopic liver transplantation. During the anhepatic phase, plasma amino acid levels rose except for tryptophan. Cystine and alanine (Ala) increased significantly to 210 +/- 28% (n = 20, mean +/- SEM) and 203 +/- 11% from preoperative values (100%), respectively. In animals successfully surviving without hepatic insufficiency after transplantation of fresh livers (n = 7), plasma amino acid levels were restored to preoperative values within 3 hr following reperfusion. On the other hand, in animals that died from hepatic insufficiency within 5 days after grafting of warm ischemically damaged livers (n = 8), plasma amino acids, especially Ala, phenylalanine, total free plasma amino acids, and aromatic amino acids progressively increased to 216 +/- 25, 274 +/- 36, 152 +/- 15, and 152 +/- 15% at 3 hr after reperfusion. These were significantly higher compared to those of the group of animals transplanted with fresh livers (P less than 0.01-0.05). Furthermore, higher values were found in those dogs transplanted with warm ischemically damaged livers surviving for shorter periods. Also in dogs that died from hepatic insufficiency within 8 hr after grafting of livers preserved for 24 hr (n = 5), amino acid levels were at high values at 3 hr. These results suggest that in animals having good graft function, plasma amino acid levels are restored to preoperative values by 3 hr after reperfusion. In other cases, primary nonfunction should be strongly suspected after liver transplantation.

Intraductal carcinoma in a surgically resected pancreas with chronic pancreatitis

SummaryA 59-yr-old Japanese male presented with epigastralgia. Endoscopic retrograde cholangiopancreatography (ERCP) revealed narrowing of the inferior common bile duct and protein plugs in the main pancreatic duct. He was diagnosed as suffering from chronic pancreatitis with suspicion of a pancreatic head tumor, and a pancreatoduodenectomy was performed. Histologically, a diffuse chronic pancreatitis was evident in the resected pancreas. Although no tumors were seen in the head portion of the pancreas around the inferior common bile duct, an intraductal carcinoma was found in the second branch of Santorini’s duct. Precancerous alteration of the duct epithelium, presenting papillary hyperplasia, and atypical hyperplasia were observed in areas continuous with the intraductal carcinoma. Immunohistochemically, carcinoembronic antigen (CEA) was specifically expressed in atypical hyperplasia and intraductal carcinoma, but not in papillary hyperplasia.

Agarose-microeneapsulated Islet Xenotransplantation.

Discordant異種膵ラ島移植におけるアガロースマイクロカプセル化 (MC (+)) と15-Deoxyspergualin (DSG) 投与の併用効果につき検討した.雑種成犬単離ラ島を5%アガロースハイドロゲルにて, マイクロカプセル化した.6,000個膵ラ島を糖尿病BALB/cマウス, またはNODマウスの腹腔内に異種移植した.Mc (+) ラ島の平均生着日数はそれぞれ37.8日, 30.6日であり, Mc (-) 群に対し有意の生着延長効果を認めた.Mc (+) に少量のDSG投与を加えることにより, 平均生着日数は76.3日, 75.3日とさらに著明に延長した.Mc (+) 群のマウス抗イヌ抗体価レベルは, DSG投与の有無にかかわらず, 移植後50%以上となる場合も認めたが, 正常血漿糖濃度が維持され, 抗体はMc (+) ラ島に傷害をあたえなかった.アガロースマイクロカプセル化とDSG投与の併用による著明な生着延長効果を認め, 将来の異種ラ島移植におけるバイオ人工膵の有用性を示した.